Fantastic Voyage

A 21st-century journey into the brain

We have come a long way since ancient Egyptians believed the heart was the seat of
thinking and mental functions—or since the Neolithic Era, when trephination (the process
of drilling holes in the human skull) was a commonplace treatment for seizures, migraines,
and mental health disorders.

Thanks in large part to advances in imaging techniques, we now have substantive knowledge
of how the human brain is organized anatomically and functionally. The amygdala, for
example, located deep within the temporal lobe, performs a primary role in the processing
of memory and emotions.

Wernicke’s area and Broca’s area, each located in the cerebral cortex, guide our understanding
and use of language. Additionally, the development of amazing new techniques such
as “brainbow,” which enables researchers to identify individual neurons and trace
their activity over time, has expanded our knowledge and understanding of the brain
at a cellular level.

It is what lies between the circuitry and the actions that remains elusive. How do
cells and synapses come together in an integrated fashion to represent a memory, to
form organized speech, or to experience a perception? How do genes and the environment
shape the developing brain? What goes wrong to then cause the hundreds of diseases
that affect the nervous system, including Alzheimer’s disease and stroke? And, most
importantly, how do we use what we have learned to improve health throughout life?

With the help of insightful investigators from multiple fields­—key among them public
health—we can begin to understand what triggers disease and/or drives its progression,
and why some individuals are more vulnerable to certain diseases than others. The
abundance of new information at our fingertips is daunting. But it also represents
huge promise, as these studies by U-M SPH researchers show. —Kristen Gibson, MPH ’14

The Three-Pound Giant

The average human brain weighs less than a bag of sugar. But as new public health
research reveals, the tiny powerhouse inside our skulls has a huge impact on our health
and well-being.

Better Management of Brain Tumor Treatments

Biostatistician Tim Johnson and a team of researchers in the U-M Department of Radiology
are analyzing MRI measures in an effort to find quicker ways to determine the efficacy
of chemo- and radiation therapies in battling high-grade gliomas, a type of brain
tumor. Currently, it takes months to know if a given therapy is working. Johnson and
his colleagues hope to speed up that process so that physicians and patients can have
results within weeks, not months. It’s potentially life-saving research, Johnson notes,
because the sooner physicians know a treatment is not working, the sooner they can
alter an existing therapy or introduce a new one.

MS: A Better Understanding

A chronic, often disabling disease, multiple sclerosis attacks the body’s nervous
system by damaging nerve fibers and their protective coating. Symptoms can be as mild
as numbness or as severe as paralysis or vision loss, and vary depending on the disease
subtype. Typically, people with MS must wait months or years before knowing their
subtype—but biostatistician Tim Johnson and a team of neuroradiologists hope to change
that. By analyzing MRI data from people who have MS and correlating those images with
outcomes from two primary functional tests, Johnson and his colleagues hope to find
ways to predict MS subtypes so that newly diagnosed individuals know what to expect
and can plan accordingly.

Targeted Nanotherapy

Chemo- and radiation therapies attack—and damage—both cancerous and noncancerous cells.
But what if a therapy could target cancerous cells only? SPH toxicologist Martin Philbert
and U-M’s Raoul Kopelman are developing a nanotherapy consisting of “smart” polymer
nanoparticles, or bubbles, that exclusively target cancerous brain tumors in rats.
When the solution is injected into the bloodstream, the polymer bubbles bond with
the tumors. The scientists then illuminate the tumors with a laser guide. “Within
ten minutes all of the cells in the tumor are dead or dying,” Philbert says. “And
because the polymer solution is biodegradable, it disappears within hours.”

The nanotherapy has been shown to be effective with cancer cells that don’t respond
to conventional therapies. To date Philbert and Kopelman have tested their nanotherapy
exclusively on rats; the next step will be clinical trials.

Strokes and Disparities

Through a large population-based study of stroke in south Texas, SPH epidemiologist
Lynda Lisabeth is endeavoring to find out why Mexican Americans have higher stroke
rates than their non-Hispanic white neighbors. Her recent findings show that even
though stroke risk is decreasing in both populations, disparities persist. PhD student
Jeffrey Wing is working with Lisabeth to examine potential links between air pollution
and stroke risk in both populations. Wing says his findings to date are “suggestive
of an association,” and he wants to know whether that association is stronger among
Mexican Americans, who may be more susceptible to the effects of air pollution—including
particulate matter emitted by nearby oil refineries.

Strokes and Disparities

Through a large population-based study of stroke in south Texas, SPH epidemiologist
Lynda Lisabeth is endeavoring to find out why Mexican Americans have higher stroke
rates than their non-Hispanic white neighbors. Her recent findings show that even
though stroke risk is decreasing in both populations, disparities persist. PhD student
Jeffrey Wing is working with Lisabeth to examine potential links between air pollution
and stroke risk in both populations. Wing says his findings to date are “suggestive
of an association,” and he wants to know whether that association is stronger among
Mexican Americans, who may be more susceptible to the effects of air pollution—including
particulate matter emitted by nearby oil refineries.

Your Brain on Values

Can core values motivate physical activity? Through a collaborative study led by Emily
Falk, assistant professor of communication at the University of Pennsylvania, SPH
Professor Victor Strecher and a team of researchers are analyzing brain imagery from
individuals who recite their core values while undergoing an MRI. These individuals
then participate in a physical activity program. By measuring their physical activity
and comparing those measurements to the MRI images, the researchers hope to determine
how values motivate physical behavior. Preliminary findings indicate a strong connection.
“We’re finding that when people recite their core values, it hits a certain reward
center in the brain,” Strecher explains. “That center is a very motivating center—so
it stimulates physical activity.”

ALS and Pesticides

The most common motor neuron disease in the U.S., amyotrophic lateral sclerosis (ALS
or Lou Gehrig’s disease) is a debilitating, ultimately fatal disease. ALS causes motor
neurons to degenerate, which leads to muscle weakness and atrophy. SPH Professor Stuart
Batterman is conducting a case-control study aimed at confirming an association between
ALS and pesticide exposure. “Our study suggests a linkage between past occupational
exposure to pesticides and the development of ALS,” he explains. “This linkage has
been shown for exposures as far back as 30 years before diagnosis.” Using data from
U-M’s ALS Clinic, the researchers are analyzing blood samples for biomarkers of exposure
to pesticides, testing for a newly discovered gene that is associated with a small
fraction of ALS cases, and examining questionnaires from study participants. If he
and his team can confirm the linkage between pesticide exposure and ALS, Batterman
says it will provide “one more reason to reduce exposures or reduce the toxicity of
chemicals such as pesticides.”

Stress, Brain Function, and Obesity

Early-life stressors can impair long-term brain function, says Alison Miller, who
studies the impact of chronic stress on child development and obesity. “If you don’t
have a chance to recover from early stressors, your ability to plan and think ahead
is less likely to be well developed.” In children who’ve undergone long periods of
stress without recovery, Miller and her team have found atypical levels of the hormone
cortisol—which is released in response to stress. These same children show higher
levels of obesity. Miller theorizes that over time, their biobehavioral stress response
becomes “blunted.” She’s working to develop interventions to counteract negative social
and environmental factors in children’s lives. “The brain continues to be plastic
throughout the lifecourse,” she says. “Even though it may be more difficult to change
things later on, it’s possible.”